Claims for Patent: 10,975,046

Summary for Patent: 10,975,046

Title:	Crystal modifications of odevixibat
Abstract:	The present invention relates to crystal modifications of 1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N—{(R)-α-[N—((S)-1-carboxypropyl)carbamoyl]-4-hydroxybenzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine (odevixibat), more specifically crystal modifications 1 and 2 of odevixibat. The invention also relates to a process for the preparation of crystal modification 1 of odevixibat, to a pharmaceutical composition comprising crystal modification 1, and to the use of this crystal modification in the treatment of various conditions as described herein.
Inventor(s):	Robert Lundqvist, Ingvar Ymen, Martin Bohlin, Eva Byröd, Per-Göran Gillberg, Anna-Maria Tivert, Rikard Bryland, Ann-Charlotte Dahlquist, Jessica Elversson, Nils Ove Gustafsson
Assignee:	Eva Byroed Consulting AB , Tivert Konsult AB , Albireo AB
Application Number:	US16/508,036
Patent Claims:	1. A crystalline hydrate of odevixibat. 2. The hydrate according to claim 1, which is a channel hydrate. 3. The hydrate according to claim 1, which comprises from about 0 to about 2 moles of water associated with the crystal per mole of odevixibat. 4. The hydrate according to claim 1, which is a sesquihydrate. 5. The hydrate according to claim 1, having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 5.6±0.2, 6.7±0.2 and/or 12.1±0.2. 6. The hydrate according to claim 5, having an XRPD pattern, obtained with CuKα1-radiation, with specific peaks at °2θ positions 5.6±0.2, 6.7±0.2 and 12.1±0.2 and one or more of the characteristic peaks: 4.1±0.2, 4.6±0.2, 9.3±0.2, 9.4±0.2 and 10.7±0.2. 7. The hydrate according to claim 5, having a crystallinity of greater than about 99%. 8. A mixed solvate of odevixibat, containing about two moles of water per mole of odevixibat. 9. The mixed solvate according to claim 8, wherein the organic solvent is methanol, ethanol, 2-propanol, acetone, acetonitrile, 1,4-dioxane, DMF or DMSO. 10. The mixed solvate according to claim 8, wherein the organic solvent is ethanol. 11. The mixed solvate according to claim 8, having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 5.0±0.2, 5.1±0.2 and/or 11.8±0.2. 12. The mixed solvate according to claim 11, having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 5.0±0.2, 5.1±0.2, 6.4±0.2, 6.6±0.2, 9.5±0.2 and 11.8±0.2. 13. The mixed solvate according to claim 8, having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 4.8±0.2, 5.1±0.2 and/or 11.6±0.2. 14. The mixed solvate according to claim 13, having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 4.8±0.2, 5.1±0.2, 6.2±0.2, 6.67±0.2, 9.5±0.2, 11.6±0.2 and 20.3±0. 15. The mixed solvate according to claim 8, having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 5.0±0.2, 6.2±0.2, 9.4±0.2 and/or 23.9±0.2. 16. The mixed solvate according to claim 15, having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 5.0±0.2, 6.2±0.2, 9.4±0.2 and 23.9±0.2 and one or more of the characteristic peaks: 11.5±0.2, 19.5±0.2 and 20.2±0.2. 17. A process for the preparation of crystal modification 1 of odevixibat, comprising isolating crystal modification 2 of odevixibat from a solution of odevixibat in a solvent mixture comprising water and an organic solvent selected from the group consisting of methanol, ethanol, 2-propanol, acetone, acetonitrile, 1,4-dioxane, DMF and DMSO. 18. The process according to claim 17, wherein the crystal modification 2 of odevixibat is crystal modification 2A of odevixibat. 19. The process according to claim 17, wherein crystal modification 2A of odevixibat is obtained from a mixture of water and ethanol. 20. The process according to claim 19, wherein the ethanol content in the solvent mixture is about 55 to about 75% (v/v).